Mortality among individuals with congenital malformations who reach adulthood: Long-term follow-up of the Jerusalem Perinatal Study cohort

Background While risks associated with congenital anomalies (CAs) in childhood are well documented, data on the long-term impact of CAs on adult mortality are lacking. We aimed to study mortality risks in adults born with CAs using the population-based Jerusalem Perinatal Study cohort. Methods Individuals born in 1964-1976 who attained 18 years of age were followed up until 2016 or date of death (median 27.5 years). We categorized anomalies by presence/absence, severity, multiplicity, and body system affected. Cox regression models were constructed to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between CAs and all-cause mortality, adjusting for birth weight, delivery mode, maternal age, socioeconomic status at birth, maternal country of birth, and stratified by offspring sex and maternal education. Results Of the 91 459 live-born offspring, 2429 (2.7%) died before attaining age 18 years and 1454 (1.6%) died thereafter. Of 87 621 who survived to age 18, 5621 (6.4%) had CAs. Mortality was increased in those bearing any (adjusted HR (HRadj) = 1.53, CI: 1.29-1.83), single (HRadj = 1.51, CI: 1.27-1.81), severe (HRadj = 2.21, CI: 1.75-2.77), and moderate and severe malformations combined (HRadj = 2.19, CI: 1.09-4.40), when compared to individuals without anomalies. Additionally, adult mortality was increased in individuals with cardiovascular (HRadj = 4.81, CI: 2.15-10.70), gastrointestinal (HRadj = 2.74, CI: 1.47-5.11), and genitourinary anomalies (HRadj = 1.51, CI: 1.07-2.14). Conclusion Increased risks of premature mortality are observed in individuals with CA who reach adulthood and are modified by severity and the body system affected. Long-term and focused follow-up for adults with CAs is warranted.